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Gene Review

SLC6A1  -  solute carrier family 6 (neurotransmitter...

Homo sapiens

Synonyms: GABATHG, GABATR, GABT1, GAT-1, GAT1, ...
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Disease relevance of SLC6A1


Psychiatry related information on SLC6A1


High impact information on SLC6A1

  • They are members of the 12 membrane-spanning superfamily and they segregate into two groups, the Na+/glucose (SGLT1) and Na+/Cl-/GABA (GAT-1) families [4].
  • In the present experiments, the N-terminal cytoplasmic domain of the GABA transporter GAT1 regulated substrate transport rates [5].
  • The substrate-induced rate change (i) is prevented by coapplication of GAT1 antagonists, (ii) does not occur in oocytes expressing GAT1 alone, and (iii) does not occur in oocytes expressing interaction-deficient syntaxin 1A mutants [6].
  • In this study, an antibody directed against the GABA membrane transporter GAT-1 was used to label GABA axon terminals in postmortem human brains [7].
  • The high-affinity mammalian brain L-proline transporter (PROT) belongs to the GAT1 gene family, which includes Na- and Cl-dependent plasma membrane carriers for neurotransmitters, osmolites, and metabolites [8].

Chemical compound and disease context of SLC6A1


Biological context of SLC6A1


Anatomical context of SLC6A1

  • We aimed to identify the subtypes of interneurons present within GG specimens and the expression and cellular distribution patterns of GABA receptors (GABAR) and GABA transporter 1 (GAT1) [12].
  • In oocytes expressing GAT1 and syntaxin 1A, superfusion of transporter substrates increases the GAT1 transport rate [6].
  • Syntaxin 1A inhibits GABA uptake of an endogenous GABA transporter in neuronal cultures from rat hippocampus and in reconstitution systems expressing the cloned rat brain GABA transporter GAT1 [13].
  • Electron microscopic observations showed that GAT-1+ puncta were axon terminals that formed exclusively symmetric synapses [14].
  • In this study, the cellular expression of GAT-1, the main cortical GABA transporter, was investigated in the human cerebral cortex by using immunocytochemistry with affinity-purified polyclonal antibodies directed to the C-terminus of rat GAT-1 [14].

Associations of SLC6A1 with chemical compounds

  • This model (based on hydropathy analysis) was originally proposed for GAT-1 and adopted for all other members of the sodium- and chloride-dependent neurotransmitter transporter superfamily [15].
  • In lithium-containing medium, GAT-1 mediates GABA-independent currents, the relationship of which to the physiological transport process is poorly understood [16].
  • The interaction of the gamma-aminobutyric acid transporter GAT-1 with the neurotransmitter is selectively impaired by sulfhydryl modification of a conformationally sensitive cysteine residue engineered into extracellular loop IV [17].
  • The nontransportable analog SKF 100330A potently inhibits the sodium-dependent transient in the wild type GAT-1 but not in the Y140W transporter [18].
  • During perforated patch recordings, the tonic GABA current was decreased by the GAT1 antagonist SKF-89976a [19].

Physical interactions of SLC6A1


Regulatory relationships of SLC6A1

  • DPB substituted THPO displayed higher inhibitory potency than the parent compound regarding the ability to inhibit GABA uptake via GAT-1 and GAT-2 [20].

Other interactions of SLC6A1

  • When these experiments were repeated in hippocampal slices, similar results were obtained except that a GAT1- and GAT3-independent nonvesicular source(s) of GABA was found to contribute to the tonic current [19].
  • Computer-assisted analysis of the average cross-sectional somatic area of parvalbumin, calretinin and GAT-1 messenger RNA-positive neurons revealed them all to be in the range of 300 microm2 [21].
  • Tonic current induced by application of the GABA transporter GAT-1 blocker NO711 (1-[2([(diphenylmethylene)imino]oxy)ethyl]-1,2,5,6-tetrahydro-3-pyridinecarboxylic acid hydrochloride) was significantly larger in the alpha1-/-, suggesting an increase of ambient GABA concentration [22].
  • Expression of GAD65 and GAD67 mRNA in the DLPFC and in the occipital cortex was significantly elevated in patients with schizophrenia, whereas the expression of the corresponding proteins and GAT-1 mRNA was unchanged [23].
  • Taken together, the complementary immunocytochemical and electrophysiological results suggest that bullfrog Müller cells express functional GAT-1 and GAT-2, which may regulate GABAergic transmission by either taking up or releasing GABA, or both [24].

Analytical, diagnostic and therapeutic context of SLC6A1


  1. Expression of the gamma-aminobutyric acid (GABA) plasma membrane transporter-1 in monkey and human retina. Casini, G., Rickman, D.W., Brecha, N.C. Invest. Ophthalmol. Vis. Sci. (2006) [Pubmed]
  2. GAT1 and GAT3 expression are differently localized in the human epileptogenic hippocampus. Lee, T.S., Bjørnsen, L.P., Paz, C., Kim, J.H., Spencer, S.S., Spencer, D.D., Eid, T., de Lanerolle, N.C. Acta Neuropathol. (2006) [Pubmed]
  3. GABA transporters (GAT-1) in Alzheimer's disease. Nägga, K., Bogdanovic, N., Marcusson, J. Journal of neural transmission (Vienna, Austria : 1996) (1999) [Pubmed]
  4. Sodium cotransport proteins. Wright, E.M., Hager, K.M., Turk, E. Curr. Opin. Cell Biol. (1992) [Pubmed]
  5. Transport rates of GABA transporters: regulation by the N-terminal domain and syntaxin 1A. Deken, S.L., Beckman, M.L., Boos, L., Quick, M.W. Nat. Neurosci. (2000) [Pubmed]
  6. Substrates regulate gamma-aminobutyric acid transporters in a syntaxin 1A-dependent manner. Quick, M.W. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  7. A subclass of prefrontal gamma-aminobutyric acid axon terminals are selectively altered in schizophrenia. Woo, T.U., Whitehead, R.E., Melchitzky, D.S., Lewis, D.A. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  8. L-proline and L-pipecolate induce enkephalin-sensitive currents in human embryonic kidney 293 cells transfected with the high-affinity mammalian brain L-proline transporter. Galli, A., Jayanthi, L.D., Ramsey, I.S., Miller, J.W., Fremeau, R.T., DeFelice, L.J. J. Neurosci. (1999) [Pubmed]
  9. Substrate-induced regulation of gamma-aminobutyric acid transporter trafficking requires tyrosine phosphorylation. Whitworth, T.L., Quick, M.W. J. Biol. Chem. (2001) [Pubmed]
  10. Proximity of transmembrane domains 1 and 3 of the gamma-aminobutyric acid transporter GAT-1 inferred from paired cysteine mutagenesis. Zomot, E., Zhou, Y., Kanner, B.I. J. Biol. Chem. (2005) [Pubmed]
  11. SNAP-25/Syntaxin 1A Complex Functionally Modulates Neurotransmitter {gamma}-Aminobutyric Acid Reuptake. Fan, H.P., Fan, F.J., Bao, L., Pei, G. J. Biol. Chem. (2006) [Pubmed]
  12. Inhibitory networks in epilepsy-associated gangliogliomas and in the perilesional epileptic cortex. Aronica, E., Redeker, S., Boer, K., Spliet, W.G., van Rijen, P.C., Gorter, J.A., Troost, D. Epilepsy Res. (2007) [Pubmed]
  13. Protein kinase C regulates the interaction between a GABA transporter and syntaxin 1A. Beckman, M.L., Bernstein, E.M., Quick, M.W. J. Neurosci. (1998) [Pubmed]
  14. Neuronal and glial localization of GAT-1, a high-affinity gamma-aminobutyric acid plasma membrane transporter, in human cerebral cortex: with a note on its distribution in monkey cortex. Conti, F., Melone, M., De Biasi, S., Minelli, A., Brecha, N.C., Ducati, A. J. Comp. Neurol. (1998) [Pubmed]
  15. The membrane topology of GAT-1, a (Na+ + Cl-)-coupled gamma-aminobutyric acid transporter from rat brain. Bennett, E.R., Kanner, B.I. J. Biol. Chem. (1997) [Pubmed]
  16. Transmembrane domain I of the gamma-aminobutyric acid transporter GAT-1 plays a crucial role in the transition between cation leak and transport modes. Kanner, B.I. J. Biol. Chem. (2003) [Pubmed]
  17. The interaction of the gamma-aminobutyric acid transporter GAT-1 with the neurotransmitter is selectively impaired by sulfhydryl modification of a conformationally sensitive cysteine residue engineered into extracellular loop IV. Zomot, E., Kanner, B.I. J. Biol. Chem. (2003) [Pubmed]
  18. Tyrosine 140 of the gamma-aminobutyric acid transporter GAT-1 plays a critical role in neurotransmitter recognition. Bismuth, Y., Kavanaugh, M.P., Kanner, B.I. J. Biol. Chem. (1997) [Pubmed]
  19. The Transmembrane Sodium Gradient Influences Ambient GABA Concentration by Altering the Equilibrium of GABA Transporters. Wu, Y., Wang, W., Richerson, G.B. J. Neurophysiol. (2006) [Pubmed]
  20. Action of bicyclic isoxazole GABA analogues on GABA transporters and its relation to anticonvulsant activity. Bolvig, T., Larsson, O.M., Pickering, D.S., Nelson, N., Falch, E., Krogsgaard-Larsen, P., Schousboe, A. Eur. J. Pharmacol. (1999) [Pubmed]
  21. Localization of calcium-binding proteins and GABA transporter (GAT-1) messenger RNA in the human subthalamic nucleus. Augood, S.J., Waldvogel, H.J., Münkle, M.C., Faull, R.L., Emson, P.C. Neuroscience (1999) [Pubmed]
  22. Deletion of the GABA(A) receptor alpha1 subunit increases tonic GABA(A) receptor current: a role for GABA uptake transporters. Ortinski, P.I., Turner, J.R., Barberis, A., Motamedi, G., Yasuda, R.P., Wolfe, B.B., Kellar, K.J., Vicini, S. J. Neurosci. (2006) [Pubmed]
  23. GAD67 and GAD65 mRNA and protein expression in cerebrocortical regions of elderly patients with schizophrenia. Dracheva, S., Elhakem, S.L., McGurk, S.R., Davis, K.L., Haroutunian, V. J. Neurosci. Res. (2004) [Pubmed]
  24. Expression of GABA transporters on bullfrog retinal Müller cells. Zhao, J.W., Du, J.L., Li, J.S., Yang, X.L. Glia (2000) [Pubmed]
  25. A light and electron microscopic study of GAT-1-positive cells in the cerebral cortex of man and monkey. Ong, W.Y., Yeo, T.T., Balcar, V.J., Garey, L.J. J. Neurocytol. (1998) [Pubmed]
  26. Rapid substrate-induced charge movements of the GABA transporter GAT1. Bicho, A., Grewer, C. Biophys. J. (2005) [Pubmed]
  27. Molecular cloning and structure of the human (GABATHG) GABA transporter gene. Lam, D.M., Fei, J., Zhang, X.Y., Tam, A.C., Zhu, L.H., Huang, F., King, S.C., Guo, L.H. Brain Res. Mol. Brain Res. (1993) [Pubmed]
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